Composition, form of production and packaging
Tablets of blue color with white impregnations and separate impregnations of dark blue color, oval, biconcave, with a notch on one side.
levodopa 250 mg
carbidopa 25 mg
Excipients: microcrystalline cellulose, pregelatinized starch, corn starch, blue dye (indigotine E132), magnesium stearate.
10 pieces. - Blisters (10) - Cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
An antiparkinsonian preparation. Levodopa reduces the symptoms of Parkinson's disease by increasing the content of dopamine in the brain. Carbidopa, which does not penetrate the BBB, prevents extracerebral decarboxylation of levodopa, thereby increasing its amount entering the brain and converting to dopamine.
Nakom В® has a more pronounced therapeutic effect than levodopa, it provides a long-term maintenance of the therapeutic concentration of levodopa in plasma at doses that are approximately 80% lower than those required when one levodopa is used.
The effect of the drug manifests itself during the first 24 hours after the start of the procedure, sometimes after the first dose. The maximum effect is achieved within 7 days.
After ingestion of carbidopa in a single dose in patients with Parkinson's disease, T max ranges from 1.5 h to 5 h.
Metabolism and excretion
Metabolised in the liver.
Among the metabolites excreted in the urine, the main ones are alpha-methyl-3-methoxy-4-hydroxyphenylpropionic acid, as well as alpha-methyl-3.4-dihydroxyphenylpropionic acid, which constitute about 14% and 10% of excreted metabolites, respectively. In smaller amounts, two other metabolites are found. One of them is identified as 3.4-dihydroxyphenyl-acetone, the other is preliminarily as N-methyl-carbidopa. The content of each of these substances is not more than 5% of the total amount of metabolites. In the urine, unchanged carbidopa is also found. Conjugates have not been identified.
Excretion in the urine of the unchanged drug basically ends within 7 hours and is 35%.
Levodopa is rapidly absorbed from the digestive tract and is actively metabolized. Despite the fact that more than 30 different metabolites are formed, mainly levodopa is converted to dopamine, epinephrine, norepinephrine.
After oral administration of levodopa in a single dose in patients with Parkinson's disease, T max is 1.5-2 hours and is maintained at the therapeutic level for 4-6 hours.
Metabolites are rapidly excreted in the urine - within about 2 hours, about 1/3 of the dose is excreted.
T 1/2 of levodopa is about 50 minutes.
When taking a combination of carbidopa and levodopa T 1/2 levodopa increases to about 1.5 hours.
Effect of carbidopa on the metabolism of levodopa
Carbidopa increases the concentration of levodopa in the blood plasma. With the previous intake of carbidopa, the concentration of levodopa in the blood plasma is increased approximately 5-fold, and the time of maintenance of the therapeutic concentration in the plasma increases from 4 to 8 hours. With the simultaneous administration of carbidopa and levodopa, similar results were obtained.
In patients with Parkinson's disease who had previously taken carbidopa, levodopa was increased from 3 to 15 hours with levodopa in a single dose of T 1/2 levodopa. The concentration of levodopa increased at least by 3 times due to carbidopa. The concentration of dopamine and homovanilic acid in blood plasma and in urine decreases with the preliminary intake of carbidopa.
- treatment of Parkinson's disease and Parkinson's syndrome.
The optimal daily dose is determined by careful individual selection. The shape of the tablet allows you to divide it into two parts with minimal effort.
During the treatment, it may be necessary to correct both the individually selected dose and the frequency of taking the drug. As research has shown, peripheral dopa decarboxylase is saturated with carbidopa when the latter is administered at a dose of about 70-100 mg / day. Patients receiving carbidopa in a smaller dose may experience nausea and vomiting.
In the case of Nakoma, the administration of standard drugs for the treatment of parkinsonism, with the exception of those containing one levodopa, can be continued, with their doses to be recruited.
The initial dose is selected in accordance with the indications and response of the patient to treatment. The initial dose of Nacom В® is 1/2 table. 1-2 times / day.However, such a dose may not provide the optimum amount of carbidopa that the patient will need. Therefore, if necessary, add 1/2 tablet. Nakoma every day or every other day until the optimal effect is achieved. The therapeutic effect is observed on the first day, and sometimes after the first dose. The full effect of the drug is achieved within 7 days.
When switching from levodopa preparations, the administration of the latter should be stopped, at least 12 hours before the start of Nakom В® treatment (24 hours after the use of levodopa with prolonged action). The daily dose of Nacom В® should provide approximately 20% of the previous daily dose of levodopa.
For patients taking more than 1.5 g of levodopa, the initial dose of Nakoma is 1 tab. 3-4 times / day.
With maintenance therapy , if necessary, the dose of Nakoma can be increased by 1 / 2-1 tab. every day or every other day until the maximum dose is reached - 8 tablets / day. The experience of taking carbidopa in a dose of more than 200 mg / day is limited.
The maximum recommended dose of Nakom В® is 8 tab. / Day (200 mg carbidopa and 2 g levodopa). This is approximately 3 mg of carbidopa and 30 mg of levodopa per 1 kg of body weight (with a patient's body weight of 70 kg).
Most often - dyskinesia, including involuntary movements (including choreyobodnye, dystonic), as well as nausea.
Early signs on the basis of which a decision can be made to abolish the drug are muscle twitchings and blepharospasm.
From the side of the central nervous system and the peripheral nervous system: CNS, episodes of bradykinesia ("on-off" -syndrome), dizziness, drowsiness, paresthesia, episodes of psychotic conditions, including illusions, hallucinations and paranoid thinking, depression with or without suicidal intent, dementia , sleep disorders, agitation, confusion, increased libido.
In rare cases - convulsions, but a causal relationship with the use of Nakom В® is not established.
From the digestive system: possible anorexia, vomiting, bleeding from the gastrointestinal tract, exacerbation of peptic ulcer of the duodenum, diarrhea, darkening of saliva.
On the part of the body as a whole: possible fainting, chest pain.
From the cardiovascular system: arrhythmias and / or palpitations, orthostatic effects (including episodes of increase or decrease in blood pressure), phlebitis.
On the part of the hematopoiesis system: leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.
From the respiratory system: it is possible dyspnea.
Dermatological reactions: alopecia, rash, darkening of secretions of sweat glands are possible.
From the genitourinary system: darkening of urine.
Allergic reactions: angioedema, urticaria, pruritus, Shenlen-Henoch disease.
Other side effects that can occur as a result of taking levodopa:
On the part of the digestive system: dyspepsia, dry mouth, bitterness in the mouth, sialorrhea, dysphagia, bruxism, bouts of hiccough, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
From the side of metabolism: decrease or increase in body weight, swelling.
From the side of the central nervous system: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased tremor of hands, muscle cramps, trismus, activation of latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation , instability of gait.
On the part of the senses: diplopia, blurred vision, dilated pupils, oculogic crises.
From the genitourinary system: delay urination, urinary incontinence, priapism.
Other: hoarseness of voice, malaise, "hot flashes" of blood to the skin of the face, neck and thorax, dyspnoea, malignant melanoma.
On the part of laboratory indicators: increased activity of alkaline phosphatase, AST, ALT, LDH, an increase in bilirubin, urea nitrogen in plasma, an increase in serum creatinine, hyperuricemia, a positive Coombs test, a decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, erythrocyturia.
Drugs containing carbidopa and levodopa can cause a false positive reaction to ketone bodies in the urine if test strips are used to determine ketonuria. This reaction will not change after boiling urine samples. False negative results can be obtained by using a glucose oxidase method for determining glucosuria.
- an angle-closure glaucoma;
- Melanoma established or suspected;
- skin diseases of unknown etiology;
- simultaneous administration with nonselective MAO inhibitors (administration of MAO inhibitors should be discontinued 2 weeks before the start of Levodopa);
- Hypersensitivity to the components of the drug.
With caution should apply the drug in severe diseases of the cardiovascular system, incl. with myocardial infarction with heart rhythm disturbances (in the anamnesis), heart failure, severe diseases of the respiratory system, including bronchial asthma, convulsive seizures (in the anamnesis), including epileptic, erosive-ulcerative lesions of the digestive tract (due to the possibility of bleeding from the upper gastrointestinal tract ), decompensated diseases of the endocrine system, including diabetes mellitus, severe renal insufficiency, severe hepatic insufficiency, open-angle glaucoma.
PREGNANCY AND LACTATION
The influence of Nakoma on the course of pregnancy in women is unknown. In experimental studies , it was found that the combination of levodopa and carbidopa causes visceral and skeletal changes in animals. Therefore, the use of the drug is possible only if the expected benefit of therapy for the mother exceeds the potential risk to the fetus.
It is not known whether levodopa and carbidopa are excreted in breast milk. There is one report on excretion of levodopa with breast milk in a nursing mother with Parkinson's disease. Therefore, due to the possible serious adverse effect of the drug on the newborn and taking into account the importance of the therapy for the mother, if the drug is needed during lactation, the question should be either to stop breastfeeding or to cancel the Nacom В® drug.
APPLICATION FOR FUNCTIONS OF THE LIVER
Caution should be used in patients with severe renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Caution should be used in patients with severe hepatic insufficiency.
APPLICATION FOR CHILDREN
The safety of the drug in children of young and middle age is not established.
It is not recommended to appoint NacomВ® to children and adolescents under the age of 18 years .
As with the use of levodopa, when Nakoma is prescribed to patients who underwent myocardial infarction and who have atrial, nodular or ventricular arrhythmias, a thorough preliminary examination is necessary. In such patients, it is necessary to monitor cardiac activity, especially when administering the first dose and during the dose selection period.
Patients with open-angle glaucoma Nakom В® should be administered with caution and under the condition of constant monitoring of intraocular pressure during treatment.
Since both therapeutic and side effects are more likely to occur when using a combination of carbidopa and levodopa than one levodopa, careful monitoring is necessary during the dose selection period for patients. In particular, Nacom В® causes involuntary movements more often than levodopa. The appearance of involuntary movements may require a dose reduction. An early indication of an excessive dose in some patients may be blepharospasm.
If the therapeutic response to levodopa is unstable, and the manifestations and symptoms of Parkinson's disease are not controlled throughout the day, switching to NakomВ® usually reduces the variation in response to the drug.
Due to the reduction of certain negative effects caused by the preparation of levodopa, NacomВ® provides patients with an adequate reduction in the symptoms of Parkinson's disease.
Nakom В® is also indicated for patients with Parkinsonism taking vitamin preparations containing pyridoxine hydrochloride (vitamin B 6 ).
Nakom В® is not recommended for the elimination of extrapyramidal disorders caused by medications.
Nakom В® can be given to patients already receiving drugs containing only levodopa, however, the intake of levodopa should be discontinued, at least 12 hours before treatment with Nacom В® . Nakom В® should be given in doses that provide approximately 20% of the previous dose of levodopa.
In patients who have previously taken levodopa, dyskinesia can be observed, because carbidopa allows more levodopa to reach the brain, and thus, more dopamine is formed. The appearance of dyskinesia may require a dose reduction.
Like levodopa, Nacom В® can cause involuntary movements or mental disorders. It is assumed that these reactions are due to an increase in the content of dopamine in the brain. These phenomena may require a dose reduction. All patients taking Nacom В® should be supervised in connection with the possibility of developing a depressive state with suicidal tendencies. Patients who have experienced psychosis require a cautious approach when selecting therapy.
Caution should be given to Nacom В® and psychotropic drugs.
With the sudden withdrawal of antiparkinsonian drugs, a symptom complex was described that resembled a malignant neuroleptic syndrome, including muscle rigidity, fever, mental disorders, and an increase in the concentration of serum CK. Therefore, a thorough examination of patients during the period of a sharp reduction in the dose of Nakoma В® or its cancellation is necessary, especially if the patient receives neuroleptics. As with levodopa, during long-term treatment with Nakoma, periodic monitoring of liver, hematopoietic, cardiovascular and renal functions is recommended.
If general anesthesia is required, Nacom В® can be taken as long as the patient is allowed oral fluid and medication.
If the treatment is temporarily interrupted, then Nakoma can be resumed in the usual dose as soon as the patient is able to take the drug inside.
Use in Pediatrics
The safety of the drug in children of young and middle age is not established.
It is not recommended to appoint NacomВ® to children and adolescents under the age of 18 years .
Symptoms: increased side effects.
Treatment: close monitoring and ECG monitoring should be provided to identify possible arrhythmias, and adequate antiarrhythmic therapy should be provided if necessary. It is necessary to take into account the possibility that along with the drug Nakom В® the patient took other medications.
When using Nakoma, patients who received antihypertensive therapy had symptomatic orthostatic hypotension (at the beginning of treatment with Nacom В® in such cases, correction of the dose of an antihypertensive drug may be required).
With simultaneous application of levodopa with MAO inhibitors (except for MAO type B inhibitors), circulatory disorders are possible (administration of MAO inhibitors should be discontinued 2 weeks before the start of levodopa). This is due to the accumulation under the influence of levodopa dopamine and norepinephrine, the inactivation of which is inhibited by MAO inhibitors. As a result, there is a high probability of excitation, increased blood pressure, tachycardia, facial flushing and dizziness.
There are separate reports of adverse reactions, including increased blood pressure and dyskinesia in the case of combined use of tricyclic antidepressants and Nakoma.
Bioavailability of carbidopa and / or levodopa decreases with the simultaneous use of iron sulfate or iron gluconate.
With simultaneous application of levodopa with beta-adrenostimulants, ditiline and means for inhalation anesthesia, an increased risk of heart rhythm disturbances is possible.
Dopamine D 2 -receptor antagonists (eg, phenothiazines, butyrophenones and risperidone), as well as isoniazid, can reduce the therapeutic effect of levodopa.
There are reports of a blocking of the positive therapeutic effect of levodopa in Parkinson's disease as a result of taking phenytoin and papaverine. Patients taking these drugs concomitantly with Nacom В® require careful monitoring to detect the reduction in therapeutic effect in a timely manner.
Lithium preparations increase the risk of dyskinesias and hallucinations.
With the simultaneous use of methyldopa increases the side effect of Nakoma.
Simultaneous use of tubocurarine increases the risk of arterial hypotension.
The absorption of levodopa may be impaired in some patients on high protein diet as levodopa competes with certain amino acids.
Carbidopa inhibits the action of pyridoxine hydrochloride (vitamin B 6 ), which accelerates the biotransformation of levodopa to dopamine in peripheral tissues.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored in a dry, protected from light, out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years. Do not use after the expiry date printed on the package.